title: Ophthalmic manifestations in a Chinese family with familial amyloid polyneuropathy due to a TTR Gly83Arg mutation.
abstract: OBJECTIVE
  To describe the characteristic ophthalmic phenotypes of a large Chinese family with familial amyloid polyneuropathy due to a missense mutation in transthyretin (TTR) (c.307 C>G).
  
  
  METHODS
  Twenty-seven individuals (12 affected, 15 unaffected) from a five-generation Chinese family underwent general medical examination and comprehensive ophthalmic examination, including best correct visual acuity, intraocular pressure measurements, Schirmer test, slitlamp examination, fundoscopy, and ocular ultrasonography. Histological examination of vitreous biopsies using Congo red staining and immunohistochemistry was performed. Cardiovascular magnetic resonance (CMR), electrocardiogram, and echocardiogram were used to evaluate cardiac amyloidosis. Electromyography was used to evaluate nerve function. All four exons of TTR were amplified by PCR, sequenced using a Bigdye terminator v3.1 cycle sequencing kit and analyzed on an ABI 3700XL Genetic Analyzer.
  
  
  RESULTS
  All 12 affected individuals in the family had ocular manifestations, including severe vitreous opacities, secondary glaucoma, xerophthalmia, dyscoria, and attenuated retinal arteries. Congo red staining demonstrated amyloid deposits in the vitreous, and immunohistochemical staining confirmed the deposition of TTR proteins in the vitreous. Twelve individuals had polyneuropathy, and electromyography detected functional damage in peripheral nerves. One individual was diagnosed with cardiac amyloidosis by CMR. Direct sequencing revealed the heterozygous missense mutation in TTR (c.307 C>G p.Gly83Arg) in all 12 affected individuals. The mutation co-segregated with the disease phenotype and was absent in 100 normal controls.
  
  
  CONCLUSIONS
  Vitreous opacity is very common in patients with the TTR Gly83Arg mutation; other clinical characteristics associated with the mutation include polyneuropathy and cardiac amyloidosis.
authors.affiliation: 1] Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China [2] Department of Ophthalmology, Hainan Branch of Chinese PLA General Hospital, Sanya, China.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Chinese PLA Medical School, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology and Hepatology, Hainan Branch of Chinese PLA General Hospital, Sanya, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology and Shiley Eye Center, University and California San Diego, La Jolla, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: Collage of life Science, Nankai University, Tianjin, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Ophthalmology, Chinese PLA Medical School, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000328:Adult; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics; D002681:China; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D004585:Electrooculography; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons / Q000235:genetics; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007429:Intraocular Pressure; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D014792:Visual Acuity; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D011228:Prealbumin